Liquid-phase processes are important over a wide range of areas in science and technology, including biological activity in cells, biomineralization, the low-cost synthesis of nanoparticles and electrochemical reactions for energy storage. Electron microscopy opens a unique window into structures and processes in the liquid phase, as it provides a combination of temporal and spatial resolution that is not achievable with other techniques. Transmission electron microscopy (TEM) of samples in liquid has a history stretching back as far as the earliest electron microscopes [A1]. But, over the past decade, electron microscopy of liquid samples has experienced a surge of interest, generated by advances in thin-film [A2] and microchip technology [A3]. Recent applications have included the imaging of labeled structures within whole cells [A4], electrochemical reactions [A3, A5] and solution-phase nanoparticle growth [A6].
For example, to develop new therapeutics, an important prerequisite is knowledge about the functioning of molecules inside cells, such as proteins and DNAs, and to learn about the interactions of cells with other organisms, such as viruses. Time-resolved confocal microscopy aims to image protein distributions and functions in living cells [1], leading to conclusions about the functioning of proteins inside live cells. However, light microscopy has a diffraction limited spatial resolution of at most 200 nm, such that processes cannot be resolved on a molecular level. Several techniques exist providing higher spatial resolution. Examples are stimulated emission depletion (STED) [2] and photoactivated localization microscopy (PALM) [3]. But those techniques still have a limited resolution on live cells and require special fluorescent labels.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.